Interaction of selected divalent metal ions with human ataxin-3 Q36

The mode of interaction of ataxin-3 Q36 (AT-3 Q36) with selected endogenous and exogenous metal ions, namely, Zn(2+), Cu(2+), Ni(2+), and Cd(2+), was examined. Metal-ion-induced structural changes of the protein were monitored by fluorescence as well as Fourier transform Raman spectroscopy. We found that the cations tested lead to a decrease in alpha-helical content and a concurrent increase in beta-sheet as well as undefined (beta-turn and random-coil) structures. The most evident effect was observed for copper and nickel cations. After titration with these cations, the AT3 Q36 secondary structure content (27% alpha-helices in the presence of either ion, 31 and 27% beta-sheets for Cu(2+) and Ni(2+), respectively) was similar to that observed for the aggregated form of the protein (27% alpha-helices, 36% beta-sheets). Using the 1-anilinonaphthalene-8-sulfonate hydrophobic fluorescence probe, we showed that the presence of the metal ions tested led to the formation of solvent-exposed hydrophobic patches of AT-3 Q36, and that such an effect decreased with increasing ionic radius.

The mode of interaction of ataxin-3 Q36 (AT-3 Q36) with selected endogenous and exogenous metal ions, namely, Zn2+, Cu2+, Ni2+, and Cd2+, was examined. Metal-ion-induced structural changes of the protein were monitored by fluorescence as well as Fourier transform Raman spectroscopy. We found that the cations tested lead to a decrease in alpha-helical content and a concurrent increase in beta-sheet as well as undefined (beta-turn and random-coil) structures. The most evident effect was observed for copper and nickel cations. After titration with these cations, the AT3 Q36 secondary structure content (27% alpha-helices in the presence of either ion, 31 and 27% beta-sheets for Cu2+ and Ni2+, respectively) was similar to that observed for the aggregated form of the protein (27% alpha-helices, 36% beta-sheets). Using the 1-anilinonaphthalene-8-sulfonate hydrophobic fluorescence probe, we showed that the presence of the metal ions tested led to the formation of solvent-exposed hydrophobic pa...